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Chimpanzee simian-type blood groups: reproducibility of formerly described antisera and demonstration of new blood groups Oc and Pc1.

A chimpanzee of simian-type blood groups V.A, cef, G, H, L was isoimmunized with the red cells of another chimpanzee of simian-type V.B, cef, G, H, 1 in order to obtain antibodies of specificity anti-Bc, originally produced in another chimpanzee in 1964. In addition to the desired anti-Bc, the immunized chimpanzee produced also three other antibodies; anti-Yc cross-reactive with chimpanzee red cells of the simian-type Bc and/or Dc, a potent cold autoantibody reactive for red cells of all chimpanzees tested, and 'new' antibodies anti-Oc and anti-Pc. This study confirms the reproducibility of results obtained over a period of 13 years.

Animals↗

Seasonal changes in the techniques employed by wild chimpanzees in the Mahale Mountains, Tanzania, to feed on termites (Pseudacanthotermes spiniger).

During a short period, wild chimpanzees of group K in the Mahale Mountains employ a set of several techniques, including tool use, to feed on one species of termite (Pseudacanthotermes spiniger). They appear to use each technique appropriately according to phenological changes in the prey insect's activities. The chimpanzees also ingest small pieces of soil from the tower of P. spiniger's mound throughout the year. Geophagy presumably makes them visually and tactually aware of the phenological changes of the termite's reproductive cycle. Analyses of fecal samples from the chimpanzees indicate interannual fluctuations in the amount of termites ingested. On the other hand, the chimpanzees of group B, ranging to the north of group K, utilize a fishing technique to obtain another type of termite (Macrotermes?herus) on a large scale during the first half of the wet season. Fecal analysis data show that chimpanzees of group B consume far more termites than those of group K. The probability that the same or similar tool-using techniques as fishing may be employed in feeding on different types of insects by chimpanzees of different unit groups according to subtle local differences in the insect fauna of their home ranges is discussed.

Animals↗

Characteristics of ground reaction forces in normal and chimpanzee-like bipedal walking by humans.

Bipedal walking by common chimpanzees is known to differ both kinematically and kinetically from human bipedalism, in particular by the adoption of flexed-knee gaits and characteristically single-peaked vertical ground reaction force curves. This study provides a test of the proposition that the two former mechanical characteristics are functionally related. Further, it examines the pattern of forces occurring during normal human bipedal walking at slow, normal and fast velocities; and during walking imitating bipedal walking of the common chimpanzee, by both male and female human adults and children. The data suggest naturally reared chimpanzees walk with greater lateral forces than do adult humans walking erect. Women show greater variance in force parameters than do men; and children more than do adults, but men walk with greater vertical accelerations of the centre of mass, and sharper peaks of sagittal acceleration and deceleration than women. Data from both forceplate and pressure-pad records suggest that young children (and a chimpanzee for which forceplate data was available) accelerate using the heel, rather than the anterior part of the foot. A principal component analysis of Fourier coefficients for the force curves shows that forces produced by adults imitating chimpanzee gaits are intermediate between those produced in normal human gait and those produced by 'real' chimpanzees, confirming a functional connection between knee and hip kinematics during bipedal walking and the shape of the vertical ground reaction force curve. Human flexed-knee, flexed-hip walking is found to produce in-phase fluctuations in potential and kinetic energies, preventing the energy exchange which obtains in erect walking. Finally, computer simulations of bipedal walking indicate that kinematics are more influential determinants of ground reaction forces than are body parameters.

Adult↗

Comparative analysis of cancer genes in the human and chimpanzee genomes.

BACKGROUND: Cancer is a major medical problem in modern societies. However, the incidence of this disease in non-human primates is very low. To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes. RESULTS: This analysis has revealed that all examined human cancer genes are present in chimpanzee, contain intact open reading frames and show a high degree of conservation between both species. However, detailed analysis of this set of genes has shown some differences in genes of special relevance for human cancer. Thus, the chimpanzee gene encoding p53 contains a Pro residue at codon 72, while this codon is polymorphic in humans and can code for Arg or Pro, generating isoforms with different ability to induce apoptosis or interact with p73. Moreover, sequencing of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that prematurely truncates the co-regulated NBR2 gene. CONCLUSION: These data suggest that small differences in cancer genes, as those found in tumor suppressor genes, might influence the differences in cancer susceptibility between human and chimpanzee. Nevertheless, further analysis will be required to determine the exact contribution of the genetic changes identified in this study to the different cancer incidence in non-human primates.

Animals↗

Directionality of point mutation and 5-methylcytosine deamination rates in the chimpanzee genome.

BACKGROUND: The pattern of point mutation is important for studying mutational mechanisms, genome evolution, and diseases. Previous studies of mutation direction were largely based on substitution data from a limited number of loci. To date, there is no genome-wide analysis of mutation direction or methylation-dependent transition rates in the chimpanzee or its categorized genomic regions. RESULTS: In this study, we performed a detailed examination of mutation direction in the chimpanzee genome and its categorized genomic regions using 588,918 SNPs whose ancestral alleles could be inferred by mapping them to human genome sequences. The C-->T (G-->A) changes occurred most frequently in the chimpanzee genome. Each type of transition occurred approximately four times more frequently than each type of transversion. Notably, the frequency of C-->T (G-->A) was the highest in exons among the genomic categories regardless of whether we calculated directly, normalized with the nucleotide content, or removed the SNPs involved in the CpG effect. Moreover, the directionality of the point mutation in exons and CpG islands were opposite relative to their corresponding intergenic regions, indicating that different forces govern the nucleotide changes. Our analysis suggests that the GC content is not in equilibrium in the chimpanzee genome. Further quantitative analysis revealed that the 5-methylcytosine deamination rates at CpG sites were highly dependent on the local GC content and the lengths of SNP flanking sequences and varied among categorized genomic regions. CONCLUSION: We present the first mutational spectrum, estimated by three different approaches, in the chimpanzee genome. Our results provide detailed information on recent nucleotide changes and methylation-dependent transition rates in the chimpanzee genome after its split from the human. These results have important implications for understanding genome composition evolution, mechanisms of point mutation, and other genetic factors such as selection, biased codon usage, biased gene conversion, and recombination.

5-Methylcytosine↗

Evolution of candidate transcriptional regulatory motifs since the human-chimpanzee divergence.

BACKGROUND: Despite the recent completion of the chimpanzee genome project, few functionally significant sequence differences between humans and chimpanzees have thus far been identified. Alteration in transcriptional regulatory mechanisms represents an important platform for evolutionary change, suggesting that a significant proportion of functional human-chimpanzee sequence differences may affect regulatory elements. RESULTS: To explore this hypothesis, we performed genome-wide identification of conserved candidate transcription-factor binding sites that have evolved since the divergence of humans and chimpanzees. Analysis of candidate transcription-factor binding sites conserved between mouse and chimpanzee yet absent in human indicated that loss of candidate transcription-factor binding sites in the human lineage was not random but instead correlated with the biologic functions of associated genes. CONCLUSION: Our data support the notion that changes in transcriptional regulation have contributed to the recent evolution of humans. Moreover, genes associated with mutated candidate transcription-factor binding sites highlight potential pathways underlying human-chimpanzee divergence.

Animals↗

Serum concentrations of relaxin, chorionic gonadotropin, estradiol-17 beta, and progesterone during the reproductive cycle of the chimpanzee (Pan troglodytes).

Levels of serum relaxin were measured by a specific RIA and correlated with serum patterns of estradiol-17 beta, progesterone, LH, or cCG during a single menstrual cycle in each of 10 female chimpanzees, and throughout 24 pregnancies in 21 chimpanzees. Significant concentrations of relaxin, higher than those reported for the human being, were detected in serum of nonpregnant chimpanzees during the late luteal phase of the menstrual cycle. During pregnancy in the chimpanzee, serum relaxin concentrations, exceeding levels found during the luteal phase, were highest during the first third of gestation, and declined thereafter. Although the absolute concentrations were higher, the patterns of relaxin secretion throughout the reproductive cycle in chimpanzees was qualitatively very similar to that observed in other primates, including the human being. The chimpanzee should thus provide a useful model for examining the role of relaxin in human reproduction.

Animals↗

Comparison of DNA and protein polymorphisms between humans and chimpanzees.

To examine the nucleotide diversity at silent (synonymous + intron + untranslated) and non-silent (nonsynonymous) sites in chimpanzees and humans, genes at six nuclear loci from two chimpanzees were sequenced. The average silent diversity was 0.19%, which was significantly higher than that in humans (0.05%). This observation suggests a significantly larger effective population size and a higher extent of neutral polymorphism in chimpanzees than in humans. On the other hand, the non-silent nucleotide diversity is similar in both species, resulting in a larger fraction of neutral mutations at non-silent sites in humans than in chimpanzees. Other types of polymorphism data were collected from the literature or databases to examine whether or not they are consistent with the nuclear DNA sequence polymorphism observed here. The nucleotide diversity at both silent and non-silent sites in mitochondrial (mt) DNA genes was compatible with that of the nuclear genes. Microsatellite loci showed a similar high extent of heterozygosity in both species, perhaps due to the combined effect of a high mutation rate and a recent population expansion in humans. At protein loci, humans are more heterozygous than chimpanzees, and the estimated fraction of neutral alleles in humans (0.84) is much larger than that in chimpanzees (0.26). These data show that the neutral fraction in non-silent changes is relatively large in the human population. This difference may be due to a relaxation of the functional constraint against proteins in the human lineage. To evaluate this possibility, it will be necessary to examine nucleotide sequences in relation to the physiological or biochemical properties of proteins.

Aldehyde Reductase↗

Chimpanzee responding during matching to sample: control by exclusion.

Three chimpanzees performed a computerized matching-to-sample task in which samples were photographs of items and comparison stimuli were geometric symbols called lexigrams. In Experiment 1, samples were either defined (i.e., they represented items that were associated already with a specific lexigram label by the chimpanzees) or undefined (i.e., they did not have an already learned association with a specific lexigram). On each trial, the foil (incorrect) comparison could be either a defined or an undefined lexigram. All 3 chimpanzees selected the correct comparison for undefined samples at a level significantly better than chance only when the foil comparison was defined. In Experiment 2, three comparisons were presented on each trial, and in Experiment 3, four comparisons were presented on each trial. For Experiments 2 and 3, the foil comparisons consisted of either defined or undefined comparisons or a mixture of both. For these two experiments, when the chimpanzees were presented with an undefined sample, they typically made selections of only undefined comparisons. These data indicate that the chimpanzees responded through use of exclusion. A final experiment, however, indicated that, despite the use of exclusion to complete trials with undefined samples correctly, the chimpanzees did not learn new associations between undefined samples and comparisons.

Animals↗

Fibrinogen receptor antagonist-induced thrombocytopenia in chimpanzee and rhesus monkey associated with preexisting drug-dependent antibodies to platelet glycoprotein IIb/IIIa.

Most clinical trials with fibrinogen receptor antagonists (FRAs) have been associated with thrombocytopenia. This report describes the occurrence of thrombocytopenia in one chimpanzee and one rhesus monkey upon administration of potent FRAs. Chimpanzee A-264 experienced profound thrombocytopenia on two occasions immediately upon intravenous administration of two different potent FRAs, L-738, 167 and L-739,758. However, an equally efficacious antiaggregatory dose of another potent antagonist, L-734,217, caused no change in platelet count. These compounds did not affect platelet count in five other chimpanzees or numerous other nonhuman primates. Flow cytometric analysis showed drug-dependent antibodies (DDAbs) in the plasma of chimpanzee A-264 that bound to platelets of chimpanzees, humans, and all other primates tested only in the presence of the compounds that induced thrombocytopenia. Rhesus monkey 94-R021 experienced thrombocytopenia upon administration of a different antagonist, L-767,679, and several prodrugs that are converted into the active form, L-767,679, in the blood. More than 20 other FRAs, including those that induced thrombocytopenia in chimpanzee A-264, had no effect on platelet count in this monkey. Flow cytometric measurements again identified DDAbs that reacted with platelets of all primates tested and required the presence of L-767,679. Screening for DDAbs in the plasma of 1,032 human subjects with L-738, 167 and L-739,758 demonstrated that the incidence of these preexisting antibodies in this population was 0.8% +/- 0.6% and 1.1% +/- 0.6%, respectively.

Animals↗

HE2/EP2, an androgen-dependent protein from the epididymis of the chimpanzee, Pan troglodytes.

A cDNA clone of chimpanzee EP2 was obtained from epididymal RNA by RT-PCR and was sequenced. Chimpanzee EP2 and human HE2 cDNA were > 99% identical and the proteins were 100% identical. The derived amino acid sequence of chimpanzee EP2 showed a consensus sequence for a leader peptide typical of secreted proteins. Northern blot analysis indicated that expression of the gene encoding chimpanzee EP2 is specific to the epididymis and not to other chimpanzee tissues examined. RT-PCR and northern blot analysis of epididymides recovered from an androgen deprived adult male chimpanzee showed that the expression of EP2 is androgen dependent.

Androgens↗

Experimental onchocerciasis in chimpanzees. Cell-mediated immune responses, and production and effects of IL-1 and IL-2 with Onchocerca volvulus infection.

Nine of eighteen chimpanzees inoculated with infective third-stage larvae of Onchocerca volvulus developed patent infection with microfilariae in skin biopsies. In all infected chimpanzees the in vitro cellular reactivity to O. volvulus adult worm-derived Ag (OvAg) increased significantly after exposure to third-stage larvae. However, during prepatency the in vitro cellular responses to OvAg decreased gradually in subsequently mf positive (patent) animals, and returned with patency to values not different to those before infection. In non-patent chimpanzees cellular responses remained significantly higher than before infection. Stimulation of PBMC in vitro with bacterial Ag and mitogen did not show any differences between the experimental groups through 20 months p.i. The addition of exogenous IL-2 did not restore the impaired responses of PBMC to OvAg in patent animals. Exogenous IL-2 elicited an additive increase of the cellular response to OvAg in nonpatent, and a mitogenic effect to OvAg in patent animals. Selective depletion of adherent, suppressor/cytotoxic (CD8+), NK cells (CD16+) and the use of autologous serum had no effect on antigenic and mitogenic cellular responsiveness. OvAg-induced IL-2 production decreased after patency, whereas, IL-1 production was significantly greater in both patent and nonpatent than in control chimpanzees. In summary, these data demonstrate that experimental O. volvulus infection in chimpanzees stimulated a substantial cell-mediated immune response. In patent chimpanzees an OvAg-specific cellular hyporesponsiveness occurred before onset of patency, possibly due to decreased IL-2 production and responsiveness.

Animals↗

Symbolic cross-modal transfer in two species of chimpanzees.

2 common chimpanzees and 1 pygmy chimpanzee, all of whom were proficient lexigram symbol users, were tested on symbolic cross-modal tasks. Previous cross-modal work with nonhuman primates has been limited to nonsymbolic matching tasks. None of these chimpanzees received any advance training on cross-modal tasks prior to the testing reported here. The common chimpanzees, Sherman and Austin, were tested on visual to haptic, visual-symbolic to haptic, haptic to visual-symbolic, and olfactory to visual-symbolic matching tasks. The pygmy chimpanzee, Kanzi, was tested on auditory-symbolic to pictorial and auditory-symbolic to visual-symbolic matching tasks. All subjects were able to match stimuli across the tested dimensions with no training. These results indicate that chimpanzees who have received symbol training can perform symbolic cross-modal tasks similar to those that are typically used with human subjects. These tasks require not only cross-modal associations but also the transformation of information from symbolic to representational modes.

Animals↗

Superiority of the chimpanzee animal model to study the pathogenicity of known Mycoplasma pneumoniae and reputed mycoplasma pathogens.

As far as we know, humans are the only known natural hosts for M. pneumoniae disease. Whereas volunteer studies have provided useful data on the pathogenesis of disease and efficacy of vaccines, experimentally inducing disease in humans raises serious ethical questions and has become increasingly difficult to defend. Thus, there is a genuine need for a satisfactory animal model to study M. pneumoniae disease. Using the cotton rat and developing chick embryo models, Eaton and co-workers (9-13) have clearly shown that the infectious "Eaton agent" was the cause of primary atypical pneumonia. After the causative agent was identified as M. pneumoniae (14), more definite and quantitative studies were possible. The hamster animal model has provided most of our information on the pathogenicity of strains, the pathogenesis of disease and the potency of inactivated vaccines. However, protective data obtained in hamsters immunized with the TS mutant vaccines did not correlate with data obtained in humans, raising concern regarding the use of the hamster animal model to evaluate the potency of live TS vaccines. The chimpanzee animal model has a number of advantages. Chimpanzees become clinically ill, show positive X-ray findings, and develop cold agglutinin titers. In fact, the experimentally induced disease in chimpanzees is remarkably similar to naturally occurring primary atypical pneumonia in patients. Because of the close genomic relationship, immunologic reagents prepared and used for human studies can also be used successfully in chimpanzee studies. The chimpanzee model also has some serious disadvantages. They are expensive to house and maintain and are generally not available to the scientific community. Nonetheless, chimpanzees are probably the best, most meaningful animal models established thus far to examine the infectious process, the immune response and the pathogenesis of this disease and to determine approaches to effective therapy and immunization of diseases produced by known pathogens, like M. pneumoniae, as well as reputed mycoplasma pathogens, such as M. genitalium and M. hominis.

Animals↗

Reproduction in wild gorillas and some comparisons with chimpanzees.

Information was collected over a period of almost 12 years on the gorillas of the Virunga Volcanoes region of Rwanda and Zaire, most of it collected since September 1972. Comparisons were made with the Gombe Stream chimpanzee population (values in parentheses). Gorilla females matured at about 8 years (compared with 9-10 years for the chimpanzee) and first bred at 10-11 years (11-12 years). Males started to breed later, possibly at 15 years (about 13 years). Oestrous periods of female gorillas lasted for about 2 days (10 days) and oestrous cycles for about 30 days (36 days). Gestation in the gorilla lasts 255 days (228 days). Intervals between surviving offspring in the Virunga study groups was about 4 1/2 (5 1/2 years) but in the whole Virunga population was nearer 8 years. Lactational amenorrhoea lasted about 2 1/2 years (3 1/2 years). In gorillas and chimpanzees there were about 3 cycles to conception after parturition and females probably produce in their lifetime about 3 offspring that survive to adulthood. A successful male's productivity is greater. Mortality of immature gorillas was about 40% (50%). Initiation of courtship is generally by the female in gorillas but the male in chimpanzees. Copulation in gorillas lasts for about 1 1/2 min (7 sec) and occurs at a rate of once every 3 h when a female is in oestrus (once in 2 h). Interference in copulation is more common in the chimpanzee than the gorilla, but competition between individual males is more intense in gorilla populations. Females of both species can clearly exercise their preferences for particular males. The observed differences between the species in courtship and mating behaviour can be related to differences in the number of males available to and competing for oestrous females: in the loose multi-male chimpanzee community there is more advantage to males in initiating copulation and mating frequently and efficiently, and to females in advertising oestrus, than in the relatively stable one-male mating system of the gorilla.

Animals↗

Chimpanzee MHC class I A locus alleles are related to only one of the six families of human A locus alleles.

There are nearly 50 alleles at the highly polymorphic HLA-A class I locus that fall into six distinct families. To determine the allelic repertoire and the mechanism of generation of diversity of the A locus in primates we have analyzed A locus alleles from 28 apparently unrelated chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). We have, therefore, compared the sequences of 19 HLA-A homologues from chimpanzees and bonobos to 42 HLA-A sequences. HLA-A homologues were well preserved in chimpanzees and bonobos with very few new substitutions present in the A locus alleles of both species of chimpanzee. Surprisingly, all chimpanzees and bonobos expressed A locus alleles related to only one of the six families of human HLA-A alleles. This suggests that the common ancestor of these two species either passed through a genetic bottleneck or that selection has favored the maintenance of the HLA-A1, -A3, -A11 family in chimpanzees.

Alleles↗

Hepatitis B subunit vaccine: a preliminary report of safety and efficacy tests in chimpanzees.

The 22 nm spherical form of hepatitis B surface antigen was purified from the serum or plasma of chronic carriers of the antigen. Antigens of subtypes ayw and adr were individually prepared by isopycnic banding in cesium chloride followed by rate zonal separation in sucrose. Each preparation was stabilized with human serum albumin, and aliquots were inactivated with 1:2000 formalin at 37 C for 96 hours. The potency and immunogenicity of each preparation were determined: both antigenicity and immunogenicity were retained by the preparations following purification and inactivation. Seronegative chimpanzees were vaccinated with the antigen preparations. None of the vaccinated chimpanzees developed evidence of infection with hepatitis B virus during the follow-up period. Twenty-four weeks after vaccination vaccinated and control chimpanzees were inoculated with live hepatitis B virus. Control chimpanzees developed hepatitis associated with HBs Ag seven and nine weeks following challenge. In contrast, none of the chimpanzees vaccinated with HBs Ag developed HBs Ag or hepatitis. Thus, hepatitis B vaccine appeared to be safe and efficacious when tested in chimpanzees.

Alanine Transaminase↗

[Cognitive activity during the recognition of a different number of objects in the adolescent chimpanzee].

The ability of adolescent chimpanzee (5-7 years old) to recognise and generalize flat pictures of discrete amounts has been studied. A set of tasks (19 signal pairs) with pictures of different number of objects was used. Situational conditional reflexes of chimpanzee were developed in conditions of free behavior. Chimpanzee were taught to choose a large number of pictures. Reversion ability at conversion of signal value of irritants was examined. It is shown that chimpanzee are able to transfer the early developed knowledge to choose larger picture to larger number of objects. It points to rather developed function of generalization, and ability to make abstracts. Resolution of tasks with reversion appeared to be difficult for chimpanzee. Correlation between the ability to solve tasks of different complexity, latent period of choice and etiological indexes is revealed. Both common regularities and individual differences in formation of complex behaviour of chimpanzee are established.

Animals↗